Unique human immune signature of Ebola virus disease in Guinea

Paula Ruibal, Lisa Oestereich, Anja Ludtke, Beate Becker-Ziaja, David M Wozniak, Romy Kerber, Misa Korva, Mar Cabeza-Cabrerizo, Joseph A Bore, Fara Raymond Koundouno, Sophie Duraffour, Romy Weller, Anja Thorenz, Eleonora Cimini, Domenico Viola, Chiara Agrati, Johanna Repits, Babak Afrough, Lauren Cowley, Didier NgaboJulia Hinzmann, Marc Mertens, Ines Vitoriano, Christopher H Logue, Jan Peter Boettcher, Elisa Pallasch, Andreas Sachse, Amadou Bah, Katja Nitzsche, Eeva Kuisma, Janine Michel, Tobias Holm, Elsa-Gayle Zekeng, Isabel Garcia-Dorival, Roman Wolfel, Kilian Stoecker, Erna Fleischmann, Thomas Strecker, Anotonino Di Caro, Tatjana Avsic-Zupanc, Andreas Kurth, Silvia Meschi, Stephane Mely, Edmund Newman, Anne Bocquin, Zoltan Kis, Anne Kelterbaum, Peter Molkenthin, Fabrizio Carletti, Jasmine Portmann, Svenja Wolff, Concetta Castilletti, Gordian Schudtt, Alexandra Fizet, Lisa J Ottowell, Eva Herker, Thomas Jacobs, Birte Kretschmer, Ettore Severi, Nobila Ouedraogo, Mar Lago, Anabel Negredo, Leticia Franco, Pedro Anda, Stefan Schmiedel, Benno Kreuels, Dominic Wichmann, Marylyn M Addo, Ansgar W Lohse, Hilde De Clerck, Carolina Nanclares, Sylvie Jonckheere, Michel Van Herp, Armand Sprecher, Gao Xiaojiang, Mary Carrington, Osvaldo Miranda, Carlos M Castro, Martin Gabriel, Patrick Drury, Pierre Formenty, Boubacar Diallo, Lamine Koivogui, N'Faly Magassouba, Miles W Carroll, Stephan Gunther, Cesar Munoz-Fontela

Research output: Contribution to journalLetter

61 Citations (Scopus)

Abstract

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
Original languageEnglish
Pages (from-to)100-104
JournalNature
Volume533
Publication statusPublished - 4 May 2016

Cite this

Ruibal, P., Oestereich, L., Ludtke, A., Becker-Ziaja, B., Wozniak, D. M., Kerber, R., ... Munoz-Fontela, C. (2016). Unique human immune signature of Ebola virus disease in Guinea. Nature, 533, 100-104.

Unique human immune signature of Ebola virus disease in Guinea. / Ruibal, Paula; Oestereich, Lisa; Ludtke, Anja; Becker-Ziaja, Beate; Wozniak, David M; Kerber, Romy; Korva, Misa; Cabeza-Cabrerizo, Mar; Bore, Joseph A; Koundouno, Fara Raymond; Duraffour, Sophie; Weller, Romy; Thorenz, Anja; Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Repits, Johanna; Afrough, Babak; Cowley, Lauren; Ngabo, Didier; Hinzmann, Julia; Mertens, Marc; Vitoriano, Ines; Logue, Christopher H; Boettcher, Jan Peter; Pallasch, Elisa; Sachse, Andreas; Bah, Amadou; Nitzsche, Katja; Kuisma, Eeva; Michel, Janine; Holm, Tobias; Zekeng, Elsa-Gayle; Garcia-Dorival, Isabel; Wolfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Di Caro, Anotonino; Avsic-Zupanc, Tatjana; Kurth, Andreas; Meschi, Silvia; Mely, Stephane; Newman, Edmund; Bocquin, Anne; Kis, Zoltan; Kelterbaum, Anne; Molkenthin, Peter; Carletti, Fabrizio; Portmann, Jasmine; Wolff, Svenja; Castilletti, Concetta; Schudtt, Gordian; Fizet, Alexandra; Ottowell, Lisa J; Herker, Eva; Jacobs, Thomas; Kretschmer, Birte; Severi, Ettore; Ouedraogo, Nobila; Lago, Mar; Negredo, Anabel; Franco, Leticia; Anda, Pedro; Schmiedel, Stefan; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M; Lohse, Ansgar W; De Clerck, Hilde; Nanclares, Carolina; Jonckheere, Sylvie; Van Herp, Michel; Sprecher, Armand; Xiaojiang, Gao; Carrington, Mary; Miranda, Osvaldo; Castro, Carlos M; Gabriel, Martin; Drury, Patrick; Formenty, Pierre; Diallo, Boubacar; Koivogui, Lamine; Magassouba, N'Faly; Carroll, Miles W; Gunther, Stephan; Munoz-Fontela, Cesar.

In: Nature, Vol. 533, 04.05.2016, p. 100-104.

Research output: Contribution to journalLetter

Ruibal, P, Oestereich, L, Ludtke, A, Becker-Ziaja, B, Wozniak, DM, Kerber, R, Korva, M, Cabeza-Cabrerizo, M, Bore, JA, Koundouno, FR, Duraffour, S, Weller, R, Thorenz, A, Cimini, E, Viola, D, Agrati, C, Repits, J, Afrough, B, Cowley, L, Ngabo, D, Hinzmann, J, Mertens, M, Vitoriano, I, Logue, CH, Boettcher, JP, Pallasch, E, Sachse, A, Bah, A, Nitzsche, K, Kuisma, E, Michel, J, Holm, T, Zekeng, E-G, Garcia-Dorival, I, Wolfel, R, Stoecker, K, Fleischmann, E, Strecker, T, Di Caro, A, Avsic-Zupanc, T, Kurth, A, Meschi, S, Mely, S, Newman, E, Bocquin, A, Kis, Z, Kelterbaum, A, Molkenthin, P, Carletti, F, Portmann, J, Wolff, S, Castilletti, C, Schudtt, G, Fizet, A, Ottowell, LJ, Herker, E, Jacobs, T, Kretschmer, B, Severi, E, Ouedraogo, N, Lago, M, Negredo, A, Franco, L, Anda, P, Schmiedel, S, Kreuels, B, Wichmann, D, Addo, MM, Lohse, AW, De Clerck, H, Nanclares, C, Jonckheere, S, Van Herp, M, Sprecher, A, Xiaojiang, G, Carrington, M, Miranda, O, Castro, CM, Gabriel, M, Drury, P, Formenty, P, Diallo, B, Koivogui, L, Magassouba, NF, Carroll, MW, Gunther, S & Munoz-Fontela, C 2016, 'Unique human immune signature of Ebola virus disease in Guinea', Nature, vol. 533, pp. 100-104.
Ruibal P, Oestereich L, Ludtke A, Becker-Ziaja B, Wozniak DM, Kerber R et al. Unique human immune signature of Ebola virus disease in Guinea. Nature. 2016 May 4;533:100-104.
Ruibal, Paula ; Oestereich, Lisa ; Ludtke, Anja ; Becker-Ziaja, Beate ; Wozniak, David M ; Kerber, Romy ; Korva, Misa ; Cabeza-Cabrerizo, Mar ; Bore, Joseph A ; Koundouno, Fara Raymond ; Duraffour, Sophie ; Weller, Romy ; Thorenz, Anja ; Cimini, Eleonora ; Viola, Domenico ; Agrati, Chiara ; Repits, Johanna ; Afrough, Babak ; Cowley, Lauren ; Ngabo, Didier ; Hinzmann, Julia ; Mertens, Marc ; Vitoriano, Ines ; Logue, Christopher H ; Boettcher, Jan Peter ; Pallasch, Elisa ; Sachse, Andreas ; Bah, Amadou ; Nitzsche, Katja ; Kuisma, Eeva ; Michel, Janine ; Holm, Tobias ; Zekeng, Elsa-Gayle ; Garcia-Dorival, Isabel ; Wolfel, Roman ; Stoecker, Kilian ; Fleischmann, Erna ; Strecker, Thomas ; Di Caro, Anotonino ; Avsic-Zupanc, Tatjana ; Kurth, Andreas ; Meschi, Silvia ; Mely, Stephane ; Newman, Edmund ; Bocquin, Anne ; Kis, Zoltan ; Kelterbaum, Anne ; Molkenthin, Peter ; Carletti, Fabrizio ; Portmann, Jasmine ; Wolff, Svenja ; Castilletti, Concetta ; Schudtt, Gordian ; Fizet, Alexandra ; Ottowell, Lisa J ; Herker, Eva ; Jacobs, Thomas ; Kretschmer, Birte ; Severi, Ettore ; Ouedraogo, Nobila ; Lago, Mar ; Negredo, Anabel ; Franco, Leticia ; Anda, Pedro ; Schmiedel, Stefan ; Kreuels, Benno ; Wichmann, Dominic ; Addo, Marylyn M ; Lohse, Ansgar W ; De Clerck, Hilde ; Nanclares, Carolina ; Jonckheere, Sylvie ; Van Herp, Michel ; Sprecher, Armand ; Xiaojiang, Gao ; Carrington, Mary ; Miranda, Osvaldo ; Castro, Carlos M ; Gabriel, Martin ; Drury, Patrick ; Formenty, Pierre ; Diallo, Boubacar ; Koivogui, Lamine ; Magassouba, N'Faly ; Carroll, Miles W ; Gunther, Stephan ; Munoz-Fontela, Cesar. / Unique human immune signature of Ebola virus disease in Guinea. In: Nature. 2016 ; Vol. 533. pp. 100-104.
@article{e48a5ec5dd2149e2839961cf3a5733b6,
title = "Unique human immune signature of Ebola virus disease in Guinea",
abstract = "Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.",
author = "Paula Ruibal and Lisa Oestereich and Anja Ludtke and Beate Becker-Ziaja and Wozniak, {David M} and Romy Kerber and Misa Korva and Mar Cabeza-Cabrerizo and Bore, {Joseph A} and Koundouno, {Fara Raymond} and Sophie Duraffour and Romy Weller and Anja Thorenz and Eleonora Cimini and Domenico Viola and Chiara Agrati and Johanna Repits and Babak Afrough and Lauren Cowley and Didier Ngabo and Julia Hinzmann and Marc Mertens and Ines Vitoriano and Logue, {Christopher H} and Boettcher, {Jan Peter} and Elisa Pallasch and Andreas Sachse and Amadou Bah and Katja Nitzsche and Eeva Kuisma and Janine Michel and Tobias Holm and Elsa-Gayle Zekeng and Isabel Garcia-Dorival and Roman Wolfel and Kilian Stoecker and Erna Fleischmann and Thomas Strecker and {Di Caro}, Anotonino and Tatjana Avsic-Zupanc and Andreas Kurth and Silvia Meschi and Stephane Mely and Edmund Newman and Anne Bocquin and Zoltan Kis and Anne Kelterbaum and Peter Molkenthin and Fabrizio Carletti and Jasmine Portmann and Svenja Wolff and Concetta Castilletti and Gordian Schudtt and Alexandra Fizet and Ottowell, {Lisa J} and Eva Herker and Thomas Jacobs and Birte Kretschmer and Ettore Severi and Nobila Ouedraogo and Mar Lago and Anabel Negredo and Leticia Franco and Pedro Anda and Stefan Schmiedel and Benno Kreuels and Dominic Wichmann and Addo, {Marylyn M} and Lohse, {Ansgar W} and {De Clerck}, Hilde and Carolina Nanclares and Sylvie Jonckheere and {Van Herp}, Michel and Armand Sprecher and Gao Xiaojiang and Mary Carrington and Osvaldo Miranda and Castro, {Carlos M} and Martin Gabriel and Patrick Drury and Pierre Formenty and Boubacar Diallo and Lamine Koivogui and N'Faly Magassouba and Carroll, {Miles W} and Stephan Gunther and Cesar Munoz-Fontela",
year = "2016",
month = "5",
day = "4",
language = "English",
volume = "533",
pages = "100--104",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",

}

TY - JOUR

T1 - Unique human immune signature of Ebola virus disease in Guinea

AU - Ruibal, Paula

AU - Oestereich, Lisa

AU - Ludtke, Anja

AU - Becker-Ziaja, Beate

AU - Wozniak, David M

AU - Kerber, Romy

AU - Korva, Misa

AU - Cabeza-Cabrerizo, Mar

AU - Bore, Joseph A

AU - Koundouno, Fara Raymond

AU - Duraffour, Sophie

AU - Weller, Romy

AU - Thorenz, Anja

AU - Cimini, Eleonora

AU - Viola, Domenico

AU - Agrati, Chiara

AU - Repits, Johanna

AU - Afrough, Babak

AU - Cowley, Lauren

AU - Ngabo, Didier

AU - Hinzmann, Julia

AU - Mertens, Marc

AU - Vitoriano, Ines

AU - Logue, Christopher H

AU - Boettcher, Jan Peter

AU - Pallasch, Elisa

AU - Sachse, Andreas

AU - Bah, Amadou

AU - Nitzsche, Katja

AU - Kuisma, Eeva

AU - Michel, Janine

AU - Holm, Tobias

AU - Zekeng, Elsa-Gayle

AU - Garcia-Dorival, Isabel

AU - Wolfel, Roman

AU - Stoecker, Kilian

AU - Fleischmann, Erna

AU - Strecker, Thomas

AU - Di Caro, Anotonino

AU - Avsic-Zupanc, Tatjana

AU - Kurth, Andreas

AU - Meschi, Silvia

AU - Mely, Stephane

AU - Newman, Edmund

AU - Bocquin, Anne

AU - Kis, Zoltan

AU - Kelterbaum, Anne

AU - Molkenthin, Peter

AU - Carletti, Fabrizio

AU - Portmann, Jasmine

AU - Wolff, Svenja

AU - Castilletti, Concetta

AU - Schudtt, Gordian

AU - Fizet, Alexandra

AU - Ottowell, Lisa J

AU - Herker, Eva

AU - Jacobs, Thomas

AU - Kretschmer, Birte

AU - Severi, Ettore

AU - Ouedraogo, Nobila

AU - Lago, Mar

AU - Negredo, Anabel

AU - Franco, Leticia

AU - Anda, Pedro

AU - Schmiedel, Stefan

AU - Kreuels, Benno

AU - Wichmann, Dominic

AU - Addo, Marylyn M

AU - Lohse, Ansgar W

AU - De Clerck, Hilde

AU - Nanclares, Carolina

AU - Jonckheere, Sylvie

AU - Van Herp, Michel

AU - Sprecher, Armand

AU - Xiaojiang, Gao

AU - Carrington, Mary

AU - Miranda, Osvaldo

AU - Castro, Carlos M

AU - Gabriel, Martin

AU - Drury, Patrick

AU - Formenty, Pierre

AU - Diallo, Boubacar

AU - Koivogui, Lamine

AU - Magassouba, N'Faly

AU - Carroll, Miles W

AU - Gunther, Stephan

AU - Munoz-Fontela, Cesar

PY - 2016/5/4

Y1 - 2016/5/4

N2 - Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

AB - Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

M3 - Letter

VL - 533

SP - 100

EP - 104

JO - Nature

JF - Nature

SN - 0028-0836

ER -